Clinical features of Japanese type 1 autoimmune hepatitis patients with zone III necrosis

Aim: In Caucasians in northern Europe and North America, type 1 autoimmune hepatitis is characterized by susceptibility to human leukocyte antigens DR3 and DR4, and patients with zone III necrosis more frequently have an acute onset of the disease and a lower frequency of cirrhosis than those without. In Japanese patients, however, type 1 autoimmune hepatitis is primarily associated with DR4, and there are almost no DR3-positive patients. Thus, the clinical features of Japanese patients with type 1 autoimmune hepatitis and zone III necrosis may be different from those reported previously for Caucasians. Methods: We investigated 160 consecutive patients with type 1 autoimmune hepatitis (20 males and 140 females; median age, 55 years; range, 16-79 years). Results: Forty-seven patients (29%) had zone III necrosis, and these patients had lower serum levels of albumin and higher serum levels of total bilirubin, aspartate aminotransferaseand alanine aminotransferase. Histologically, zone III necrosis was found more frequently in patients with acute hepatitis than in those with chronic hepatitis. However, there was no difference in the frequency of cirrhosis between patients with and without zone III necrosis. In addition, normalization of serum alanine aminotransferase levels within six months after the introduction of corticosteroid treatment was slightly more frequent in patients with zone III necrosis (95% vs. 88%). Conclusion: In Japanese patients, zone III necrosis may reflect not only acute autoimmune hepatitis, but also acute exacerbation of pre-existing chronic disease. Furthermore, patients with zone III necrosis may respond better to corticosteroid treatment than those without.     

A prospective and comparative cohort study on efficacy and drug resistance during long-term lamivudine treatment for various stages of chronic hepatitis B and cirrhosis

Background and Aims: A prospective , non‐randomized cohort study on long‐term lamivudine treatment , comparing efficacy, drug resistance, and prognosis for various stages of chronic hepatitis B virus (HBV)–related liver disease was performed to elucidate the significance and indication of lamivudine for individual patients at each stage of disease. Methods: A total of 158 cases consisting of 87 chronic hepatitis, 28 compensated cirrhosis, and 43 decompensated cirrhosis, with serum HBV‐DNA > 5 log₁₀ copies/mL and with elevated alanine aminotransferase (ALT) over twice the upper normal limit or complications of hepatic insufficiency, were administered 100 mg of lamivudine daily and monitored for HBV markers, biochemistry, and prognosis. Results: Lamivudine reduced HBV‐DNA and ALT equally in all groups. Serum albumin, prothrombin time (%), and platelet count increased in all groups. The increased margin of albumin was the highest in the decompensated cirrhosis and higher in the compensated cirrhosis than the chronic hepatitis groups. Cumulative incidence of virologic breakthrough was 16%, 42%, 49%, and 53% at 12, 24, 36, and 48 months, respectively, and the strongest predictive factor for lamivudine resistance was persistent HBV‐DNA at 3 months. Ascites, encephalopathy, and jaundice improved in the majority of patients with decompensated cirrhosis. On the other hand, hepatic failure developed or deteriorated in 10 patients after virologic breakthrough, and nine of them had decompensated cirrhosis. Conclusions: Lamivudine was effective in reducing HBV‐DNA and improving hepatic reserve at all stages and was most beneficial and significant for decompensated cirrhosis. Meanwhile, close monitoring of viral load and immediate rescue treatment for lamivudine resistance is necessary to prevent hepatic failure in decompensated cirrhosis.     

Baseline factors and very early viral response (week 1) for predicting sustained virological response in telaprevir-based triple combination therapy for Japanese genotype 1b chronic hepatitis C patients: a multicenter study

Background

Genetic polymorphisms near Interleukin 28B (IL28B) (rs8099917) and a rapid virological response (RVR) have been reported as predictors for a sustained virological response (SVR) to telaprevir (TVR)-based triple combination therapy. However, the association between SVR and viral kinetics earlier than week 4 after initiation of therapy remains unclear. Thus, we evaluated the SVR prediction ability of baseline factors and reduced hepatitis C virus (HCV) RNA levels at week 1 after the initiation of TVR-based therapy in Japanese genotype-1b chronic hepatitis C (CHC) patients.

Methods

A total of 156 Japanese CHC patients received a 24-week regimen of TVR-based therapy. Baseline factors and reduction in HCV RNA levels at weeks 1 and 4 after the initiation of therapy were analyzed for SVR prediction.

Results

Multiple logistic regression analysis for SVR in TVR-based therapy identified the IL28B TT genotype, a reduction of ≥4.7 log₁₀IU/mL in HCV RNA levels at week 1, RVR, and treatment-naïve/relapse. Whereas the SVR rate was higher than 90 % regardless of the reduction in HCV RNA levels at week 1 in patients with the TT genotype, a reduction of ≥4.7 log₁₀IU/mL in HCV RNA levels at week 1 was the strongest predictor of SVR in patients with the non-TT genotype, as determined by multiple logistic regression analysis (P = 0.0043).

Conclusions

The IL28B TT genotype is the most important baseline factor for predicting SVR, and a ≥4.7 log₁₀IU/mL reduction in HCV RNA at week 1 is a useful very early on-treatment predictor of SVR, especially in the non-TT genotype.     

Anion gap‐opening metabolic acidosis and urinary findings in the early diagnosis of ethylene glycol poisoning: A case report

Causative agent identification is important in the treatment of poisoning. We report the case of a patient who presented with an altered level of consciousness after drinking a fluorescent pink liquid. Upon measuring the anion gap and urinary calcium oxalate level, the patient was diagnosed with early ethylene glycol poisoning.     

Factors Associated with Hepatitis B Surface Antigen Kinetics and Responses in Pegylated Interferon Alpha-2a Monotherapy for Patients with Chronic Hepatitis B

Objective Pegylated-interferon monotherapy is the standard treatment for patients with chronic hepatitis B; however, the factors associated with its therapeutic effects remain unclear. Methods Patients with chronic hepatitis B were treated with pegylated interferon α-2a for 48 weeks. We evaluated the kinetics of hepatitis B surface antigen (HBsAg) during treatment and follow-up periods and the factors associated with an HBsAg response (defined as a change in HBsAg of ≥-1 log IU/mL from baseline). Results The study population comprised 50 patients. The median baseline levels of hepatitis B virus DNA and HBsAg were 5.00 and 3.40 log IU/mL. The median values of HBsAg reduction from baseline were -0.44 (n=48), -0.41 (n=40), and -0.68 (n=11) log IU/mL at the end of treatment and at 48 and 144 weeks post-treatment, respectively. The rates of HBsAg response were 24.0% and 22.5% at the end of treatment and at 48 weeks post-treatment, respectively. A multivariate analysis identified HBsAg <3.00 log IU/mL as an independent baseline factor contributing to the HBsAg response at the end of treatment and 48 weeks post-treatment (p=1.07×10^-2 and 4.42×10^-2, respectively). There were significant differences in the reduction of the HBsAg levels at 12 weeks of treatment and in the incidence of serum ALT increase during treatment between patients with and without an HBsAg response. Conclusion These findings suggest that the baseline HBsAg level, HBsAg kinetics at 12 weeks of treatment, and ALT increase during treatment are important factors contributing to the HBsAg response in pegylated interferon α-2a monotherapy for patients with chronic hepatitis B.     

Chinese medicine induces neurite outgrowth in PC12 mutant cells incapable of differentiation

During continuous culture of neural PC12 cells, we obtained a drug-hypersensitive PC12 mutant cell that showed high stimulation of neurite outgrowth by various drugs. When several Chinese medicines such as shu-jing-huo-xie-tang and Wu-Ling-San were provided to these PC12 mutant cells, the frequency of nerve growth factor (NGF)-induced neurite outgrowth increased approximately 30-fold compared to NGF alone. Neurite outgrowth induced by NGF in PC12 cells is accompanied by sustained activation of mitogen-activated protein kinase (MAPK); however, these Chinese medicines did not induce MAPK activity. The findings thus indicate that certain Chinese medicines may induce neurite outgrowth by a novel mechanism which is distinct from the NGF-activated pathway in PC12 mutant cells.     

Pulmonary atelectasis after reconstruction with a rectus abdominis free tissue transfer

BACKGROUND: Atelectasis is one of the most common postoperative complications encountered in head and neck surgery. Risk factors include preexisting pulmonary disease, the procedure performed, and the length of anesthetic. Regional flaps used to reconstruct defects in the head and neck predispose to radiographic atelectasis. The rectus abdominis myocutaneous flap is usually transferred as a free tissue transfer. Harvesting the flap results in abdominal wall pain and postoperative splinting that may contribute to an increased development of atelectasis. To our knowledge, this issue has not been previously examined. DESIGN: Retrospective review. RESULTS: Fifty-three patients underwent rectus abdominis myocutaneous free flap reconstruction following major ablative procedures for head and neck cancer. The flap size ranged from 5 x 7 to 25 x 27 cm. Most flaps were 8 x 15 cm. The cutaneous area transferred ranged from 35 to 600 cm(2) (mean, 120 cm(2)). These patients were compared with a group of 53 patients who were matched for age, sex, length of the procedure, and stage of disease. Postoperative atelectasis was radiographically detected in 37 (70%) of the patients who underwent rectus abdominis myocutaneous free flap reconstruction vs 41 (77%) of the controls. Major atelectasis was not encountered in any patient in either group. Patients with a larger cutaneous paddle (>120 cm(2)) had a higher atelectasis score than patients with smaller cutaneous paddles (< or =120 cm(2)) (P =.02). CONCLUSIONS: The incidence of radiographic postoperative atelectasis in patients undergoing rectus abdominis myocutaneous free tissue transfer is high. The degree of atelectasis is small, and the clinical correlation and relevance are minimal.     

Possible contribution of prior hepatitis B virus infection to the development of hepatocellular carcinoma

BACKGROUND: The prevalence of prior hepatitis B virus (HBV) infection in hepatocellular carcinoma (HCC) patients and its role in hepatocarcinogenesis are not clear. The aim of the present study is to clarify the importance of prior HBV infection in development of HCC. METHODS: Of 1288 consecutive HCC patients between January 1999 and October 2002, 1008 patients were enrolled. To determine the influence of prior HBV infection in hepatitis B surface antigen (HBsAg)-negative HCC, the prevalence of antibody to hepatitis B core antigen (anti-HBc) was examined according to age, and the clinical features were compared between the anti-HBc positive and the negative groups. RESULTS: The proportion of HBsAg-negative HCC patients, HCC patients with antibody to hepatitis C virus (anti-HCV; C-HCC) and HCC patients negative for both HBsAg and anti-HCV (nBnC-HCC), increased with age. The anti-HBc-positive rates in C-HCC patients also increased with age. Those rates in nBnC-HCC patients were >50% in all age groups. Furthermore, it was found that the anti-HBc-positive rates of these patients were higher than those of corresponding control patients. Tumor size and a positive rate for vessel involvement both in C-HCC and nBnC-HCC patients were larger and higher, respectively, in anti-HBc-positive patients compared with anti-HBc-negative patients, although the difference in nBnC-HCC did not reach statistical significance because of the small numbers. These tumor characteristics were similar to those of B-HCC patients. CONCLUSION: A possible contribution of prior HBV infection to the development of HCC is indicated.